NMA Haplo or MUD BMT for Newly Diagnosed Severe Aplastic Anemia

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
• Overall Status: Completed
• CT.gov ID: NCT02833805
• Collaborator: (none)
• Enrollment: 21
• Location: 1
• Arm: 1
• Actual Duration (Months): 58
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Our primary objective is to determine if it is feasible for previously untreated severe aplastic anemia (SAA) patients to be transplanted using non-myeloablative conditioning and post transplantation cyclophosphamide.

Condition or Disease	Intervention/Treatment	Phase
Severe Aplastic Anemia; Aplastic Anemia; Bone Marrow Failure; Immunosuppression	Drug: Thymoglobulin; Drug: Fludarabine; Drug: Cyclophosphamide; Radiation: Total body irradiation; Drug: Tacrolimus; Drug: Mycophenolate mofetil	Phase 2

Detailed Description

This is a clinical trial of upfront bone marrow transplantation for patients with SAA who do not have a fully human leukocyte antigen (HLA) matched donor. The trial uses a conditioning regimen which has been successful in the refractory and relapsed setting to maximize engraftment and post transplant therapy to minimize graft versus host disease (GVHD). This would be used here in patients who have not yet undergone immunosuppressive therapy for their SAA or are thought to be unlikely to respond to immunosuppressive therapy for SAA.

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Non-Myeloablative (NMA) Conditioning and Transplantation of Partially HLA-Mismatched/Haploidentical Related or Matched Unrelated Donor (MUD) Bone Marrow for Newly Diagnosed Patients With Severe Aplastic Anemia
• Actual Study Start Date: Sep 1, 2016
• Actual Primary Completion Date: Jul 1, 2021
• Actual Study Completion Date: Jul 1, 2021

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Bone marrow transplant Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis.

Drug: Thymoglobulin; Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily; Other Names: Anti-thymocyte globulin ATG ; Drug: Fludarabine; Days -6 through -2: 30 mg/m^2 IV daily; Other Names: Fludara ; Drug: Cyclophosphamide; Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily; Other Names: Cytoxan Cy CTX ; Radiation: Total body irradiation; Day -1: 200 centigray (cGy) in a single fraction; Other Names: TBI ; Drug: Tacrolimus; Start on Day 5 through Day 365; Other Names: FK-506 FK506 Prograf ; Drug: Mycophenolate mofetil; Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day); Other Names: MMF CellCept

Outcome Measures

Primary Outcome Measures

1. Overall Survival and Engraftment at One Year [1 year]

   Number of enrolled participants who receive BMT, achieve engraftment, and are alive at one year post bone marrow transplant (BMT).

Secondary Outcome Measures

1. Overall Survival at One Year [1 year]

   Number of participants alive at one year after BMT.

2. Probability of Neutrophil Recovery as Assessed by the Number of Participants Who Have Recovered Neutrophil Counts [1 year]

   Probability of neutrophil recovery will be assessed by the number of participants who have recovered neutrophil counts at 1 year (>500 ANC).

3. Probability of Platelet Recovery as Assessed by Number of Participants Who Have Recovered Platelet Counts [1 year]

   Probability of platelet recovery will be assessed by the number of participants who have recovered platelet counts at 1 year.

4. Number of Participants Who Experience Primary Graft Failure [1 year]

   Number of participants who experience primary graft failure by one year after BMT.

5. Number of Participants Who Experience Secondary Graft Failure [1 year]

   Number of participants who experience secondary graft failure by one year after BMT.

6. Number of Participants Who Experience Grades II-IV Acute GVHD [Day 100]

   Number of participants who experience grade II, III, or IV acute GVHD by Day 100.

7. Number of Participants Who Experience Grades III-IV Acute GVHD [Day 100]

   Number of participants who experience grade III or IV acute GVHD by Day 100.

8. Number of Participants Who Experience Chronic GVHD [2 years]

   Number of participants who experience chronic GVHD by two years after BMT.

9. Number of Participants With Full Donor Chimerism [Day 60]

   Number of participants with full donor chimerism at Day 60.

10. GVHD-free Relapse-free Survival (GRFS) [1 year]

    Number of participants alive, without relapse, and without GVHD at 1 year.

11. Transplant-related Mortality [1 year]

    Number of participants deceased for reasons related to BMT at 1 year.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Confirmed diagnosis of inherited or acquired severe aplastic anemia (SAA)

• One of the following available donors:

1. HLA-haploidentical relative

2. If recipient is >= 40 years old, may use HLA-matched related donor

3. For recipients with inherited bone marrow failure syndromes (IBMFS) with clear evidence of same disorder in potential related donors, may use 10/10 matched unrelated donor

• Recipient and/or legal guardian must sign protocol informed consent

• Donor must be willing to donate bone marrow

• Left ventricular ejection fraction (LVEF) >= 40%. For recipients < 13 years old, shortening fraction >= 26% may be used instead.

• Bilirubin < 3 x upper limit of normal (ULN) for age, unless patient has Gilbert's disease

• aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 5 x ULN for age

• For patients >= 13 years old: estimated creatinine clearance > 50 mL/min using Cockcroft-Gault formula and actual body weight

• For patients >= 1 but < 13 years old: glomerular filtration rate (GFR) estimated by updated Schwartz formula >= 90 mL/min/1.73 m^{2. If estimated GFR is < 90 mL/min/1.73 m}2, 24-hour measured creatinine clearance must be > 50 mL/min/1.73 m^2.

• For patients >= 8 years old, diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) > 40%; forced expiratory volume at one second (FEV1) > 50%; forced vital capacity (FVC) > 50%

• For patients < 8 years old or unable to undergo pulmonary function testing: no evidence of dyspnea at rest; no need for supplemental oxygen; oxygen saturation > 92% on room air

• Karnofsky/Lansky status (depending on age) >= 70%

• Females and males of childbearing potential must agree to practice 2 effective methods of contraception at the same time. If unwilling, they must agree to complete abstinence.

Exclusion Criteria:

• Previous administration of immunosuppressive therapy for SAA.

• Fanconi anemia. At minimum, this diagnosis must be excluded by diepoxybutane (DEB) or equivalent testing on peripheral blood or marrow in patients < 30 years old.

• Clonal cytogenetic abnormalities consistent with pre-myelodysplastic syndrome (pre-MDS) or MDS on bone marrow examination

• Presence of anti-donor antibodies

• Prior allogeneic stem cell transplant

• Prior solid organ transplant

• Uncontrolled bacterial, viral, or fungal infection

• HIV seropositivity

• Active hepatitis B or C infection determined by serology and/or nucleic acid testing (NAT)

• Pregnancy or active breastfeeding

• Prior malignancies except: resected basal carcinoma or treated cervical carcinoma in situ; cancer treated with curative intent > 5 years previously. Other prior cancers will not be allowed unless approved by the PI.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21287

Sponsors and Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Investigators

• Principal Investigator: Amy E DeZern, MD, Johns Hopkins University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 24, 2020

More Information

Publications

None provided.

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT02833805
• Other Study ID Numbers: J1688; IRB00107139
• First Posted: Jul 14, 2016
• Last Update Posted: Jul 12, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: immunosuppression; nonmyeloablative; non-myeloablative; allogeneic; tacrolimus; bone marrow; bone marrow transplant; cyclophosphamide; thymoglobulin; ATG; fludarabine
• Additional relevant MeSH terms: Anemia; Anemia, Aplastic; Bone Marrow Failure Disorders; Pancytopenia; Mycophenolic Acid; Cyclophosphamide; Fludarabine; Tacrolimus; Thymoglobulin; Antilymphocyte Serum

Study Results

Participant Flow

Arm/Group Title	Bone Marrow Transplant
Arm/Group Description	Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as graft-versus-host disease (GVHD) prophylaxis. Thymoglobulin: Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily Fludarabine: Days -6 through -2: 30 mg/m^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 365 Mycophenolate mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
Period Title: Overall Study
STARTED	21
COMPLETED	21
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Bone Marrow Transplant
Arm/Group Description	Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Thymoglobulin: Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily Fludarabine: Days -6 through -2: 30 mg/m^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 365 Mycophenolate mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
Overall Participants	21
Age (Count of Participants)
<=18 years	7 33.3%
Between 18 and 65 years	14 66.7%
>=65 years	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	25
Sex: Female, Male (Count of Participants)
Female	8 38.1%
Male	13 61.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 4.8%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	4 19%
White	14 66.7%
More than one race	0 0%
Unknown or Not Reported	2 9.5%
Race/Ethnicity, Customized (Count of Participants)
African American	4 19%
Caucasian	14 66.7%
Other	3 14.3%
Region of Enrollment (Count of Participants)
United States	21 100%

Outcome Measures

1. Primary Outcome

Title	Overall Survival and Engraftment at One Year
Description	Number of enrolled participants who receive BMT, achieve engraftment, and are alive at one year post bone marrow transplant (BMT).
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bone Marrow Transplant
Arm/Group Description	Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Thymoglobulin: Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily Fludarabine: Days -6 through -2: 30 mg/m^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 365 Mycophenolate mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
Measure Participants	21
Count of Participants [Participants]	19 90.5%

2. Secondary Outcome

Title	Overall Survival at One Year
Description	Number of participants alive at one year after BMT.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bone Marrow Transplant
Arm/Group Description	Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Thymoglobulin: Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily Fludarabine: Days -6 through -2: 30 mg/m^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 365 Mycophenolate mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
Measure Participants	21
Count of Participants [Participants]	19 90.5%

3. Secondary Outcome

Title	Probability of Neutrophil Recovery as Assessed by the Number of Participants Who Have Recovered Neutrophil Counts
Description	Probability of neutrophil recovery will be assessed by the number of participants who have recovered neutrophil counts at 1 year (>500 ANC).
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bone Marrow Transplant
Arm/Group Description	Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Thymoglobulin: Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily Fludarabine: Days -6 through -2: 30 mg/m^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 365 Mycophenolate mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
Measure Participants	21
Count of Participants [Participants]	21 100%

4. Secondary Outcome

Title	Probability of Platelet Recovery as Assessed by Number of Participants Who Have Recovered Platelet Counts
Description	Probability of platelet recovery will be assessed by the number of participants who have recovered platelet counts at 1 year.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bone Marrow Transplant
Arm/Group Description	Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Thymoglobulin: Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily Fludarabine: Days -6 through -2: 30 mg/m^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 365 Mycophenolate mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
Measure Participants	21
Count of Participants [Participants]	20 95.2%

5. Secondary Outcome

Title	Number of Participants Who Experience Primary Graft Failure
Description	Number of participants who experience primary graft failure by one year after BMT.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bone Marrow Transplant
Arm/Group Description	Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Thymoglobulin: Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily Fludarabine: Days -6 through -2: 30 mg/m^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 365 Mycophenolate mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
Measure Participants	21
Count of Participants [Participants]	21 100%

6. Secondary Outcome

Title	Number of Participants Who Experience Secondary Graft Failure
Description	Number of participants who experience secondary graft failure by one year after BMT.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bone Marrow Transplant
Arm/Group Description	Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Thymoglobulin: Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily Fludarabine: Days -6 through -2: 30 mg/m^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 365 Mycophenolate mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
Measure Participants	21
Count of Participants [Participants]	19 90.5%

7. Secondary Outcome

Title	Number of Participants Who Experience Grades II-IV Acute GVHD
Description	Number of participants who experience grade II, III, or IV acute GVHD by Day 100.
Time Frame	Day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bone Marrow Transplant
Arm/Group Description	Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Thymoglobulin: Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily Fludarabine: Days -6 through -2: 30 mg/m^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 365 Mycophenolate mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
Measure Participants	21
Count of Participants [Participants]	4 19%

8. Secondary Outcome

Title	Number of Participants Who Experience Grades III-IV Acute GVHD
Description	Number of participants who experience grade III or IV acute GVHD by Day 100.
Time Frame	Day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bone Marrow Transplant
Arm/Group Description	Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Thymoglobulin: Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily Fludarabine: Days -6 through -2: 30 mg/m^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 365 Mycophenolate mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
Measure Participants	21
Count of Participants [Participants]	2 9.5%

9. Secondary Outcome

Title	Number of Participants Who Experience Chronic GVHD
Description	Number of participants who experience chronic GVHD by two years after BMT.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bone Marrow Transplant
Arm/Group Description	Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Thymoglobulin: Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily Fludarabine: Days -6 through -2: 30 mg/m^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 365 Mycophenolate mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
Measure Participants	21
Count of Participants [Participants]	1 4.8%

10. Secondary Outcome

Title	Number of Participants With Full Donor Chimerism
Description	Number of participants with full donor chimerism at Day 60.
Time Frame	Day 60

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bone Marrow Transplant
Arm/Group Description	Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Thymoglobulin: Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily Fludarabine: Days -6 through -2: 30 mg/m^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 365 Mycophenolate mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
Measure Participants	21
Count of Participants [Participants]	21 100%

11. Secondary Outcome

Title	GVHD-free Relapse-free Survival (GRFS)
Description	Number of participants alive, without relapse, and without GVHD at 1 year.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bone Marrow Transplant
Arm/Group Description	Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Thymoglobulin: Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily Fludarabine: Days -6 through -2: 30 mg/m^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 365 Mycophenolate mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
Measure Participants	21
Count of Participants [Participants]	19 90.5%

12. Secondary Outcome

Title	Transplant-related Mortality
Description	Number of participants deceased for reasons related to BMT at 1 year.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bone Marrow Transplant
Arm/Group Description	Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Thymoglobulin: Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily Fludarabine: Days -6 through -2: 30 mg/m^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 365 Mycophenolate mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
Measure Participants	21
Count of Participants [Participants]	2 9.5%

Adverse Events

Time Frame	Adverse events were monitored and collected from time of consent up to one year.
Arm/Group Title	Bone Marrow Transplant
Arm/Group Description	Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Thymoglobulin: Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily Fludarabine: Days -6 through -2: 30 mg/m^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 365 Mycophenolate mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
All Cause Mortality
	Bone Marrow Transplant
	Affected / at Risk (%)	# Events
Total	2/21 (9.5%)
Serious Adverse Events
	Bone Marrow Transplant
	Affected / at Risk (%)	# Events
Total	2/21 (9.5%)
Infections and infestations
Gram negative rods Bacteremia	2/21 (9.5%)
Other (Not Including Serious) Adverse Events
	Bone Marrow Transplant
	Affected / at Risk (%)	# Events
Total	0/21 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.